- Cyclothiazide
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Cyclothiazide 
Systematic (IUPAC) name 3-(bicyclo[2.2.1]hept-5-en-2-yl)-6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide Clinical data Pregnancy cat. ? Legal status ℞ Prescription only Identifiers CAS number 2259-96-3 
ATC code C03AA09 PubChem CID 2910 DrugBank DB00606 ChemSpider 4535011 UNII P71U09G5BW KEGG D01256 ChEMBL CHEMBL61593 
Chemical data Formula C14H16ClN3O4S2 Mol. mass 389.88 g/mol SMILES eMolecules & PubChem - InChI=1S/C14H16ClN3O4S2/c15-10-5-11-13(6-12(10)23(16,19)20)24(21,22)18-14(17-11)9-4-7-1-2-8(9)3-7/h1-2,5-9,14,17-18H,3-4H2,(H2,16,19,20)/t7-,8+,9?,14?/m0/s1
Key:BOCUKUHCLICSIY-QJWLJZLASA-N
(what is this?) (verify)Cyclothiazide (Anhydron, Acquirel, Doburil, Fluidil, Renazide, Tensodiural, Valmiran) is a benzothiadiazide (thiazide) diuretic and antihypertensive that was originally introduced in the United States in 1963 by Eli Lilly and was subsequently also marketed in Europe and Japan.[1][2] Related drugs include diazoxide, hydrochlorothiazide, and chlorothiazide.[3]
In 1993, it was discovered that cyclothiazide is a positive allosteric modulator of the AMPA receptor, capable of reducing or essentially eliminating rapid desensitization of the receptor, and potentiating glutamate currents by as much as 18-fold at the highest concentration tested (100 μM).[3][4][5][6] Additionally, in 2003, cyclothiazide was also found to act as a GABAA receptor negative allosteric modulator, potently inhibiting GABAA-mediated currents.[7] In animals it is a powerful convulsant, robustly enhancing epileptiform activity and inducing seizures, but without producing any apparent neuronal death.[8][9]
References
- ^ Swiss Pharmaceutical Society (2000). Index Nominum 2000: International Drug Directory (Book with CD-ROM). Boca Raton: Medpharm Scientific Publishers. pp. 1932. ISBN 3-88763-075-0. http://books.google.com/books?id=5GpcTQD_L2oC&lpg=PA287&dq=Cyclothiazide&pg=PA287#v=onepage&q=Cyclothiazide&f=false.
- ^ Sittig, Marshall (1988). Pharmaceutical manufacturing encyclopedia. Park Ridge, N.J., U.S.A: Noyes Publications. pp. 1756. ISBN 0-8155-1144-2. http://books.google.com/books?id=X2EyLsG4bcUC&lpg=PA418&dq=Cyclothiazide&pg=PA418#v=onepage&q&f=false.
- ^ a b Skolnick, Phil; Palfreyman, Michael G.; Reynolds, Ian J. (1994). Direct and allosteric control of glutamate receptors. Boca Raton: CRC Press. pp. 174. ISBN 0-8493-8307-2. http://books.google.com/books?id=Fp9RLJTt7NkC&lpg=PA34&dq=Cyclothiazide&pg=PA65#v=onepage&q=Cyclothiazide&f=false.
- ^ Yamada KA, Tang CM (September 1993). "Benzothiadiazides inhibit rapid glutamate receptor desensitization and enhance glutamatergic synaptic currents". Journal of Neuroscience 13 (9): 3904–15. PMID 8103555. http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=8103555.
- ^ Bertolino M, Baraldi M, Parenti C, et al. (1993). "Modulation of AMPA/kainate receptors by analogues of diazoxide and cyclothiazide in thin slices of rat hippocampus". Receptors & Channels 1 (4): 267–78. PMID 7915948.
- ^ Ströhle, Andreas; Bilkei-Gorzo, A.; Holsboer, Florian (2005). Anxiety and anxiolytic drugs. Berlin: Springer. pp. 566. ISBN 3-540-22568-4. http://books.google.com/books?id=RDP4_sBnsl4C&lpg=PA255&dq=Cyclothiazide&pg=PA256#v=onepage&q=Cyclothiazide&f=false.
- ^ Deng L, Chen G (October 2003). "Cyclothiazide potently inhibits gamma-aminobutyric acid type A receptors in addition to enhancing glutamate responses". Proceedings of the National Academy of Sciences of the United States of America 100 (22): 13025–9. doi:10.1073/pnas.2133370100. PMC 240738. PMID 14534329. http://www.pnas.org/cgi/pmidlookup?view=long&pmid=14534329.
- ^ Qi J, Wang Y, Jiang M, Warren P, Chen G (March 2006). "Cyclothiazide induces robust epileptiform activity in rat hippocampal neurons both in vitro and in vivo". The Journal of Physiology 571 (Pt 3): 605–18. doi:10.1113/jphysiol.2005.103812. PMC 1805799. PMID 16423850. http://www.jphysiol.org/cgi/pmidlookup?view=long&pmid=16423850.
- ^ Kong S, Qian B, Liu J, Fan M, Chen G, Wang Y (July 2010). "Cyclothiazide induces seizure behavior in freely moving rats". Brain Research 1355: 207–213. doi:10.1016/j.brainres.2010.07.088. PMC 2947190. PMID 20678492. http://linkinghub.elsevier.com/retrieve/pii/S0006-8993(10)01678-1.
Antihypertensives: diuretics (C03) Sulfonamides
(except EA)CA inhibitors (at PT)Hydrochlorothiazide# • Bendroflumethiazide • Hydroflumethiazide • Chlorothiazide • Polythiazide • Trichlormethiazide • Cyclopenthiazide • Methyclothiazide • Cyclothiazide • MebutizideThiazide-likes (primarily DCT)Quinethazone • Clopamide • Chlortalidone • Mefruside • Clofenamide • Metolazone • Meticrane • Xipamide • Indapamide • Clorexolone • FenquizonePotassium-sparing (at CD) ESC blockersOsmotic diuretics (PT, DL) VAs (DCT and CD) vaptans: Conivaptan • Mozavaptan • Satavaptan • Tolvaptan
tetracyclines: DemeclocyclineOther Symporter inhibitors Sodium chloride thiazide: Bendroflumethiazide • Chlorothiazide • Cyclopenthiazide • Cyclothiazide • Hydrochlorothiazide • Hydroflumethiazide • Methyclothiazide • Polythiazide • Trichlormethiazide
other: Chlorthalidone • MetolazoneSodium, potassium, chloride Glutamatergics Ionotropic Agonists: 5-Fluorowillardiine • AMPA • Domoic acid • Quisqualic acid; Positive allosteric modulators: Aniracetam • Cyclothiazide • CX-516 • CX-546 • CX-614 • CX-691 • CX-717 • Diazoxide • HCTZ • IDRA-21 • LY-392,098 • LY-404,187 • LY-451,395 • LY-451,646 • LY-503,430 • Oxiracetam • PEPA • Piracetam • Pramiracetam • S-18986 • Sunifiram • Unifiram
Antagonists: ATPO • Barbiturates • Caroverine • CNQX • DNQX • GYKI-52466 • NBQX • Perampanel • Talampanel • Tezampanel • Topiramate; Negative allosteric modulators: GYKI-53,655Agonists: Glutamate/acite site competitive agonists: Aspartate • Glutamate • Homoquinolinic acid • Ibotenic acid • NMDA • Quinolinic acid • Tetrazolylglycine; Glycine site agonists: ACBD • ACPC • ACPD • Alanine • CCG • Cycloserine • DHPG • Fluoroalanine • Glycine • HA-966 • L-687,414 • Milacemide • Sarcosine • Serine • Tetrazolylglycine; Polyamine site agonists: Acamprosate • Spermidine • Spermine
Antagonists: Competitive antagonists: AP5 (APV) • AP7 • CGP-37849 • CGP-39551 • CGP-39653 • CGP-40116 • CGS-19755 • CPP • LY-233,053 • LY-235,959 • LY-274,614 • MDL-100,453 • Midafotel (d-CPPene) • NPC-12,626 • NPC-17,742 • PBPD • PEAQX • Perzinfotel • PPDA • SDZ-220581 • Selfotel; Noncompetitive antagonists: ARR-15,896 • Caroverine • Dexanabinol • FPL-12495 • FR-115,427 • Hodgkinsine • Magnesium • MDL-27,266 • NPS-1506 • Psychotridine • Zinc; Uncompetitive pore blockers: 2-MDP • 3-MeO-PCP • 8A-PDHQ • Alaproclate • Amantadine • Aptiganel • ARL-12,495 • ARL-15,896-AR • ARL-16,247 • Budipine • Delucemine • Dexoxadrol • Dextrallorphan • Dieticyclidine • Dizocilpine • Endopsychosin • Esketamine • Etoxadrol • Eticyclidine • Gacyclidine • Ibogaine • Indantadol • Ketamine • Ketobemidone • Loperamide • Memantine • Meperidine (Pethidine) • Methadone • Methorphan (Dextromethorphan, Levomethorphan) • Methoxetamine • Milnacipran • Morphanol (Dextrorphan, Levorphanol) • NEFA • Neramexane • Nitrous oxide • Noribogaine • Orphenadrine • PCPr • Phencyclamine • Phencyclidine • Propoxyphene • Remacemide • Rhynchophylline • Riluzole • Rimantadine • Rolicyclidine • Sabeluzole • Tenocyclidine • Tiletamine • Tramadol • Xenon; Glycine site antagonists: ACEA-1021 • ACEA-1328 • ACPC • Carisoprodol • CGP-39653 • CKA • DCKA • Felbamate • Gavestinel • GV-196,771 • Kynurenic acid • L-689,560 • L-701,324 • Lacosamide • Licostinel • LU-73,068 • MDL-105,519 • Meprobamate • MRZ 2/576 • PNQX • ZD-9379; NR2B subunit antagonists: Besonprodil • CO-101,244 (PD-174,494) • CP-101,606 • Eliprodil • Haloperidol • Ifenprodil • Isoxsuprine • Nylidrin • Ro8-4304 • Ro25-6981 • Traxoprodil; Polyamine site antagonists: Arcaine • Co 101676 • Diaminopropane • Acamprosate • Diethylenetriamine • Huperzine A • Putrescine • Ro 25-6981; Unclassified/unsorted antagonists: Chloroform • Diethyl ether • Enflurane • Ethanol (Alcohol) • Halothane • Isoflurane • Methoxyflurane • Toluene • Trichloroethane • Trichloroethanol • Trichloroethylene • XyleneAgonists: 5-Iodowillardiine • ATPA • Domoic acid • Kainic acid • LY-339,434 • SYM-2081
Antagonists: CNQX • DNQX • LY-382,884 • NBQX • NS102 • Tezampanel • Topiramate • UBP-302; Negative allosteric modulators: NS-3763Metabotropic Agonists: Unselective: ACPD • DHPG • Quisqualic acid; mGlu1-selective: Ro01-6128 • Ro67-4853 • Ro67-7476 • VU-71; mGlu5-selective: ADX-47273 • CDPPB • CHPG • DFB • VU-1545
Antagonists: Unselective: MCPG • NPS-2390; mGlu1-selective: BAY 36-7620 • CPCCOEt • LY-367,385 • LY-456,236; mGlu5-selective: Dipraglurant • DMeOB • Fenobam • LY-344,545 • MPEP • MTEP • SIB-1757 • SIB-1893Agonists: Unselective: L-AP4; mGlu4-selective: PHCCC • VU-001,171 • VU-0155,041; mGlu7-selective: AMN082; mGlu8-selective: DCPG
Antagonists: Unselective: CPPG • MAP4 • MSOP • MPPG • MTPG • UBP-1112; mGlu7-selective: MMPIPTransporter
inhibitorsDHKA • PDC • WAY-213,613vGluTs7-CKA • Evans blueGABAergics Receptor
ligandsReuptake
inhibitorsPlasmalemmalGAT inhibitorsCI-966 • Deramciclane • EF-1502 • Gabaculine • Guvacine • Nipecotic acid • NNC 05-2090 • SKF-89976A • SNAP-5114 • TiagabineEnzyme
inhibitorsGAD inhibitorsAllylglycineGABA-T inhibitors3-Hydrazinopropionic acid • Aminooxyacetic acid • Gabaculine • Isoniazid • Phenelzine • Phenylethylidenehydrazine • Sodium valproate • Valnoctamide • Valproate pivoxil • Valproate semisodium (Divalproex sodium) • Valproic acid • Valpromide • VigabatrinOthers Glutamate • GlutamineOthersCategories:- Diuretics
- Sulfonamides
- AMPA receptor modulators
- Benzothiadiazines
- Organochlorides
- InChI=1S/C14H16ClN3O4S2/c15-10-5-11-13(6-12(10)23(16,19)20)24(21,22)18-14(17-11)9-4-7-1-2-8(9)3-7/h1-2,5-9,14,17-18H,3-4H2,(H2,16,19,20)/t7-,8+,9?,14?/m0/s1
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